ArticleInternational journal for parasitology. Drugs and drug resistance2014
Identification of β-hematin inhibitors in a high-throughput screening effort reveals scaffolds with in vitro antimalarial activity.
Article in International journal for parasitology. Drugs and drug resistance, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 48 citations in OpenAlex.
- PCA-mapping and machine learning identify multiple chemotypes with antiplasmodial, β-haematin and haemozoin formation inhibition activity.RSC medicinal chemistry · 2026Article
- Using Unbiased Chemical Proteomics Approaches to Explore the Target Landscape of the Resistance Refractory 7-Azaindole MMV022224 inACS infectious diseases · 2026Article
- Article
- Exploration of Antiplasmodium Chemical Space Identifies New Inhibitors of β-Hematin Formation from Areas of Enrichment.ChemMedChem · 2026Article
- Structure-Activity Relationships of 3-Hydroxypropanamidines (HPAs) with Potent In Vivo Antimalarial Activity.Journal of medicinal chemistry · 2025Article
- Characterizing the quick-killing mechanism of action of azithromycin analogs against malaria parasites.Antimicrobial agents and chemotherapy · 2025Article
- TKK130 is a 3-Hydroxy-Propanamidine (HPA) with Potent AntimalarialJournal of medicinal chemistry · 2025Article
- Identifying inhibitors of β-haematin formation with activity against chloroquine-resistant Plasmodium falciparum malaria parasites via virtual screening approaches.Scientific reports · 2023Article
- Adsorption to the Surface of Hemozoin Crystals: Structure-Based Design and Synthesis of Amino-Phenoxazine β-Hematin Inhibitors.ChemMedChem · 2022Article
- Heme Detoxification in the Malaria Parasite: A Target for Antimalarial Drug Development.Accounts of chemical research · 2021Review
- Artemisinin-Based Drugs Target the Plasmodium falciparum Heme Detoxification Pathway.Antimicrobial agents and chemotherapy · 2021Article
- A Diverse Range of Hemozoin Inhibiting Scaffolds Act onACS infectious diseases · 2021Article
- Correlation between anti-malarial and anti-haemozoin activities of anti-malarial compounds.Malaria journal · 2020Article
- Lapatinib, Nilotinib and Lomitapide Inhibit Haemozoin Formation in Malaria Parasites.Molecules (Basel, Switzerland) · 2020Article
- Virtual screening as a tool to discover new β-haematin inhibitors with activity against malaria parasites.Scientific reports · 2020Article
- Insights into structural and physicochemical properties required for β-hematin inhibition of privileged triarylimidazoles.RSC medicinal chemistry · 2020Article
- Antimalarial Quinoline Drugs Inhibit β-Hematin and Increase Free Hemin Catalyzing Peroxidative Reactions and Inhibition of Cysteine Proteases.Scientific reports · 2019Article
- Detection of Single-Nucleotide Polymorphism Markers of Antimalarial Drug Resistance Directly from Whole Blood.The Journal of molecular diagnostics : JMD · 2019Article
- Incorporation of an intramolecular hydrogen bonding motif in the side chain of antimalarial benzimidazoles.MedChemComm · 2019Article
- Hemozoin inhibiting 2-phenylbenzimidazoles active against malaria parasites.European journal of medicinal chemistry · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The emergence of drug resistant strains of Plasmodium spp. creates a critical need for the development of novel antimalarials. Formation of hemozoin, a crystalline heme detoxification process vital to parasite survival serves as an important drug target. The quinoline antimalarials including chloroquine and amodiaquine owe their antimalarial activity to inhibition of hemozoin formation. Though in vivo formation of hemozoin occurs within the presence of neutral lipids, the lipophilic detergent NP-40 was previously shown to serve as a surrogate in the β-hematin (synthetic hemozoin) formation process. Consequently, an NP-40 mediated β-hematin formation assay was developed for use in high-throughput screening. Here, the assay was utilized to screen 144,330 compounds for the identification of inhibitors of crystallization, resulting in 530 hits. To establish the effectiveness of these target-based β-hematin inhibitors against Plasmodium falciparum, each hit was further tested in cultures of parasitized red blood cells. This effort revealed that 171 of the β-hematin inhibitors are also active against the parasite. Dose-response data identified 73 of these β-hematin inhibitors have IC50 values ⩽5 μM, including 25 compounds with nanomolar activity against P. falciparum. A scaffold-based analysis of this data identified 14 primary scaffolds that represent 46% of the 530 total hits. Representative compounds from each of the classes were further assessed for hemozoin inhibitory activity in P. falciparum infected human erythrocytes. Each of the hit compounds tested were found to be positive inhibitors, while a negative control did not perturb this biological pathway in culture.
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